Editorial: Developmental Biology and Regulation of Osteoclasts (original) (raw)
Related papers
Mechanisms by which cells of the osteoblast lineage control osteoclast formation and activity
Journal of Cellular Biochemistry, 1994
The cells of bone are of two lineages, the osteoblasts arising from pluripotential mesenchymal cells and osteoclasts from hemopoietic precursors of the monocyte-macrophage series. Resorption of bone by the multinucleate osteoclast requires the generation of new osteoclasts and their activation. Many hormones and cytokines are able to promote bone resorption by influencing these processes, but they achieve this without acting directly on osteoclasts.
Osteoclasts: more than 'bone eaters' NIH Public Access
As the only cells definitively shown to degrade bone, osteoclasts are key mediators of skeletal diseases including osteoporosis. Bone forming osteoblasts, and hematopoietic and immune system cells, each influence osteoclast formation and function, but the reciprocal impact of osteoclasts on these cells is less well appreciated. Here, we highlight functions osteoclasts perform beyond bone resorption. First, we consider how osteoclast signals may contribute to bone formation by osteoblasts and the pathology of bone lesions, such as fibrous dysplasia and giant cell tumors. Second, we review the interaction of osteoclasts with the hematopoietic system, including the stem cell niche and adaptive immune cells. Connections between osteoclasts and other cells in the bone microenvironment are discussed within a clinically relevant framework. Bone remodeling and osteoclasts 101 Bone is a composite tissue of protein and mineral, which undergoes continual remodeling to grow, heal damage, and regulate calcium and phosphate metabolism. This remodeling process is executed by the concerted and sequential effort of bone resorbing osteoclasts and bone forming osteoblasts, acting in what has been termed the basic multicellular unit (BMU) (Figure 1A). Osteocytes, long-lived osteoblast-derived cells that reside within the bone matrix, monitor bone quality and stress, and coordinate remodeling through membrane bound and secreted factors. Skeletal integrity is maintained throughout the lifespan by matching bone formation and resorption, a process referred to as osteoclast:osteoblast 'coupling.' Coupling is thoroughly summarized in recent excellent reviews [1, 2] and in Figure 1. Osteoclasts are multinucleated giant cells that differentiate from myeloid precursors under the influence of the cytokines macrophage colony stimulating factor (MCSF) and receptor
Osteoblasts in Bone Physiology – Mini Review
Rambam Maimonides Medical Journal, 2012
Bone structural integrity and shape are maintained by removal of old matrix by osteoclasts and in-situ synthesis of new bone by osteoblasts. These cells comprise the basic multicellular unit (BMU). Bone mass maintenance is determined by the net anabolic activity of the BMU, when the matrix elaboration of the osteoblasts equals or exceeds the bone resorption by the osteoclasts. The normal function of the BMU causes a continuous remodeling process of the bone, with deposition of bony matrix (osteoid) along the vectors of the generated force by gravity and attached muscle activity. The osteoblasts are derived from mesenchymal stem cells (MSCs). Circulating hormones and locally produced cytokines and growth factors modulate the replication and differentiation of osteoclast and osteoblast progenitors. The appropriate number of the osteoblasts in the BMU is determined by the differentiation of the precursor bone-marrow stem cells into mature osteoblasts, their proliferation with subsequent maturation into metabolically active osteocytes, and osteoblast degradation by apoptosis. Thus, the two crucial points to target when planning to control the osteoblast population are the processes of cell proliferation and apoptosis, which are regulated by cellular hedgehog and Wnt pathways that involve humoral and mechanical stimulations. Osteoblasts regulate both bone matrix synthesis and mineralization directly by their own synthetic activities, and bone resorption indirectly by its paracrinic effects on osteoclasts. The overall synthetic and regulatory activities of osteoblasts govern bone tissue integrity and shape.
Advances in the Regulation of Osteoclasts and Osteoclast Functions
Journal of Dental Research, 2013
Osteoclasts are derived from mononuclear hematopoietic myeloid lineage cells, which are formed in the bone marrow and are attracted to the bloodstream by factors, including sphingsine-1 phosphate. These circulating precursors are attracted to bone surfaces undergoing resorption by chemokines and other factors expressed at these sites, where they fuse to form multinucleated bone-resorbing cells. All aspects of osteoclast formation and functions are regulated by macrophage-colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), cytokines essential for osteoclast formation and expressed by a variety of cell types, including osteoblast lineage cells. Since the discovery of RANKL in the mid-1990s, mouse genetic and molecular studies have revealed numerous signaling pathways activated by RANKL and M-CSF. More recent studies indicate that osteoclasts and their precursors regulate immune responses and osteoblast formation and functions by means of direct cell-cell ...
Archives of Biochemistry and Biophysics, 2014
The size and strength of bone is determined by two fundamental processes. One process, bone remodelling, renews the skeleton throughout life. In this process existing bone is resorbed by osteoclasts and replaced, in the same location, by osteoblasts. The other process is bone modelling, where bone formation and resorption occur at different sites so that the shape of bone is changed. Recent data suggests that both remodelling and modelling are controlled by signals between the cells that carry out these two processes. Osteoclasts both resorb bone, and provide inhibitory and stimulatory signals, including cardiotrophin-1 and sphingosine-1-kinase, to the osteoblast lineage thereby regulating their differentiation and activity on both trabecular and cortical surfaces. In addition, the osteoblast lineage, including osteoblast progenitors, matrix-producing osteoblasts, bone lining cells, and matrix-embedded osteocytes, produce both inhibitory and stimulatory factors that stimulate osteoclast differentiation. We will discuss the roles of osteoblast-and osteocyte-derived RANKL, and paracrine, autocrine and endocrine factors, such as eph-rinB2, the IL-6/gp130 family of cytokines, parathyroid hormone, and its related peptide, PTHrP. These factors not only stimulate RANKL production, but also stimulate osteoblast differentiation and activity. This review will focus on recent data, generated from pharmacological and genetic studies of mouse models and what these data reveal about these pathways at different stages of osteoblast differentiation and their impact on both bone remodelling and modelling in trabecular and cortical bone.
Osteoclast formation and differentiation: an overview
Journal of Medical and Dental Sciences, 2012
Osteoclasts are multinucleated cells of hematopoietic origin which are unique in their ability to resorb bone. Osteoclasts are generated from myeloid progenitors through a progression that involves the fusion of mononuclear precursor cells. The identification of RANK-RANKL signaling as the main signal regulating osteoclast differentiation was a major breakthrough in the bone biology field. In addition remarkable discoveries have been made to broaden the knowledge of the molecular mechanisms of osteoclast formation and differentiation. Despite the vital requirement of osteoclasts in bone modeling and remodeling, bone-related conditions like osteoporosis, Paget's disease and rheumatoid arthritis where accelerated bone resorption takes place pose a major socioeconomic burden to the society. Hence, a better understanding of the pathways leading to osteoclast differentiation is vital in successfully managing such diseases. This is an attempt to give a birds-eye-view of the players in...